The ZNF304-integrin axis protects against anoikis in cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26081979.
- Also identified by DOI 10.1038/ncomms8351 and PMC identifier 4830335.
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Abstract
Ovarian cancer (OC) is a highly metastatic disease, but no effective strategies to target this process are currently available. Here, an integrative computational analysis of the Cancer Genome Atlas OC data set and experimental validation identifies a zinc finger transcription factor ZNF304 associated with OC metastasis. High tumoral ZNF304 expression is associated with poor overall survival in OC patients. Through reverse phase protein array analysis, we demonstrate that ZNF304 promotes multiple proto-oncogenic pathways important for cell survival, migration and invasion. ZNF304 transcriptionally regulates β1 integrin, which subsequently regulates Src/focal adhesion kinase and paxillin and prevents anoikis. In vivo delivery of ZNF304 siRNA by a dual assembly nanoparticle leads to sustained gene silencing for 14 days, increased anoikis and reduced tumour growth in orthotopic mouse models of OC. Taken together, ZNF304 is a transcriptional regulator of β1 integrin, promotes cancer cell survival and protects against anoikis in OC.
Medical subject headings
- Anoikis
- Carcinoma
- Integrin beta Chains
- Ovarian Neoplasms
- Transcription Factors